Publications by authors named "Darshan Kumar"

Introduction: In contrast to Alzheimer's disease (AD), in which initial neurofibrillary tangles (NFT) are mainly limited to the (trans)entorhinal region (EC) and CA1/prosubiculum, primary age-related tauopathy (PART) has been suggested to exhibit an early predisposition to NFTs in the hippocampal CA2 subregion.

Methods: We created an artificial intelligence model that recognizes and quantifies NFTs of three different maturity levels in different hippocampal subfields. This model was applied to a population-based Vantaa 85+ cohort, including hippocampal tau-immunostained sections from 210 individuals aged ≥ 85 years.

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Cardiac manifestations are associated with Lewy body disease, but studies addressing the underlying histopathological mechanisms at the myocardial level are sparse. Here, we generated an artificial intelligence-based algorithm to quantify tyrosine hydroxylase (TH)-immunoreactive sympathetic distal axons at the myocardial level. This novel tool was applied to septal samples of the Vantaa 85 + study (n = 138), which is a population-based autopsy study representing all subjects aged 85 years or older living in the city of Vantaa (southern Finland) in 1991.

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Bone marrow cytology plays a key role for the diagnosis and classification of hematological disease and is often the first step in the acute setting of unclear cytopenia. AI applications represent a powerful tool in digital image analysis and can improve the diagnostic workflow and accuracy. The aim of this study was to develop an algorithm for the automated detection and classification of hematopoietic cells in digitized bone marrow aspirate smears for potential implementation in the clinical laboratory.

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Introduction: Nodal metastasis (NM) in sentinel node biopsies (SNB) is crucial for melanoma staging. However, an intra-nodal nevus (INN) may often be misclassified as NM, leading to potential misdiagnosis and incorrect staging. There is high discordance among pathologists in assessing SNB positivity, which may lead to false staging.

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Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively.

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Article Synopsis
  • Surgical excision is the main treatment for lentigo maligna (LM) to prevent it from turning into invasive melanoma, but evaluating the resection margins on sun-damaged skin is tough.
  • A deep learning model was created to identify melanocytes in these margins, using 353 whole slide images for training and testing, and compared its results with those of experienced dermatopathologists.
  • The AI model showed great accuracy, with an AUC of 0.84, and improved the performance of some pathologists, suggesting it could be a useful tool for assessing LM margins.
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Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins were measured using GeoMx digital spatial profiling in tissue microarrays from 100 diagnostic MCL tissues.

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Population-based cohort studies are essential for understanding the pathological basis of dementia in older populations. Previous studies have shown that limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) increases with age, but there have been only a few studies, which have investigated this entity in a population-based setting. Here we studied the frequency of LATE-NC and its associations with other brain pathologies and cognition in a population aged ≥ 85 years.

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Article Synopsis
  • Histological assessment of autoimmune hepatitis (AIH) is difficult, particularly with nonclassical features like bile-duct injury being understudied.
  • Researchers developed an AI tool, called AI(H), to analyze liver biopsy slides from patients with AIH, using 123 pre-treatment biopsies for training.
  • The AI models demonstrated high accuracy in detecting various features related to AIH, including tissue structures and immune cells, offering a more detailed and reproducible assessment compared to manual analysis.
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Droplet digital PCR (ddPCR) is a technique in which PCR reaction is divided into thousands of nanoliter-sized droplets and has proven to be a great tool in virus diagnostics. Compared to the gold standard system quantitative real-time PCR (RT-qPCR), ddPCR functions particularly well when dealing with samples with low template counts, such as viral concentration. This feature makes the technique suitable for early detection of the virus.

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Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae.

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The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression.

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Breast cancer is the most prevalent neoplasia among women, with early and accurate diagnosis critical for effective treatment. In clinical practice, however, the subjective nature of histological grading of infiltrating ductal adenocarcinoma of the breast (DAC-NOS) often leads to inconsistencies among pathologists, posing a significant challenge to achieving optimal patient outcomes. Our study aimed to address this reproducibility problem by leveraging artificial intelligence (AI).

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Objective: To determine correlation of HbA1c with serum iron and transferrin saturation in non-diabetic patients with iron deficiency.

Methods: This cross-sectional comparative study was conducted at Dr Ruth KM Pfau Civil Hospital Karachi from 15 September 2021 to 14 March 2022, on non-diabetic patients based on fasting blood sugar (FBS) of <100 mg/dl. Patients were divided into two groups.

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The activity-regulated cytoskeleton-associated (Arc) protein is essential for synaptic plasticity and memory formation. The Arc gene, which contains remnants of a structural GAG retrotransposon sequence, produces a protein that self-assembles into capsid-like structures harboring Arc mRNA. Arc capsids, released from neurons, have been proposed as a novel intercellular mechanism for mRNA transmission.

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The incidence of nonalcoholic fatty liver disease is a continuously growing health problem worldwide, along with obesity. Therefore, novel methods to both efficiently study the manifestation of nonalcoholic fatty liver disease and to analyze drug efficacy in preclinical models are needed. The present study developed a deep neural network-based model to quantify microvesicular and macrovesicular steatosis in the liver on hematoxylin-eosin-stained whole slide images, using the cloud-based platform, Aiforia Create.

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In this paper, we report a fast, linear wide-range hybrid flexible sensor based on a novel composite of strontium titanate (SrTiO) and poly 3,4 ethylenedioxythiophene polystyrene sulfonate (PEDOT: PSS) as a sensing layer. Inter-digitate electrodes (IDEs) were printed for humidity monitoring (finger: 250 µm; spacing: 140 µm; length: 8 mm) whilst a meander-based pattern was printed for the temperature measurement (meander thickness: 180 µm; spacing: 400 µm) on each side of the PET substrate using silver ink. Moreover, active layers with different concentration ratios were coated on the electrodes using a spray coating technique.

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The endoplasmic reticulum (ER) is composed of a controlled ratio of sheets and tubules, which are maintained by several proteins with multiple functions. Reticulons (RTNs), especially RTN4, and DP1/Yop1p family members are known to induce ER membrane curvature. RTN4B is the main RTN4 isoform expressed in nonneuronal cells.

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CYP2C9 is an important member of the cytochrome P450 gene family involved in the metabolism of 15% of the drugs including an oral antidiabetic agent sulfonylurea. This study aims to investigate the frequency of CYP2C9*2 and CYP2C9*3 alleles of the gene in the sulfonylurea treated diabetic subjects in Pakistan. Briefly, total 105 patients were included in the study and segregated as control (24) and test (81) based on the clinical manifestations after taking sulfonylurea.

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The endoplasmic reticulum (ER) is extensively remodeled during metazoan open mitosis. However, whether the ER becomes more tubular or more cisternal during mitosis is controversial, and dedicated factors governing the morphology of the mitotic ER have remained elusive. Here, we describe the ER membrane proteins REEP3 and REEP4 as major determinants of ER morphology in metaphase cells.

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Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules.

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Article Synopsis
  • Understanding cell and organelle structure-function relationships requires advanced 3-D imaging techniques due to their complexity.
  • A new software package has been developed to enhance the processing and analysis of large multidimensional datasets, addressing challenges in data management.
  • The open-source software allows customization and includes tutorials, making it easier for users to handle light and electron microscopy data efficiently.
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Objectives: To determine outcome in primary and secondary glomerular diseases at one year follow up.

Methods: Study design is observational cohort, done in out-patient department, Dow Iinternational Medical College, DUHS. All information gathered on a proforma.

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Objective: Vacuum assisted closure is a reported technique to manage complex wounds. We have utilized this technique by using simple locally available material in the management of our patients on outpatient basis. The objective of this study is to present our experience.

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